The invention disclosed herein relates to a tablet for delivering a pharmaceutical to a human transmucosally, particularly to such a tablet which fits between opposed oral mucosa in the lip and gingiva, to a method for administering the tablet and to a method for making the tablet. "Pharmaceutical" is used herein in a broad sense, and includes drugs, medications, etc.; where the context permits, these words are used interchangeably herein.
Considerable attention has been focused in recent years on the delivery through the oral mucosa of drugs which have a high first pass metabolism (i.e., metabolized to a large extent by the liver during the first pass therethrough and therefore do not enter the blood stream) or degrade in the gastrointestinal tract. Transmucosal delivery has also been considered for treatment of oral disorders and as a local anesthetic. See for example: Developments in Buccal Drug Delivery, M. E. de Vries et al., published in Critical Reviews in Therapeutic Drug Delivery Systems, 8(3), pp 271-303, CRC Press, Inc., 1991; Drug Delivery of Peptides: The Buccal Route, H. P. Merkle et al., published in Delivery Systems for Peptine Drugs, E. Tumlinson and S. S. Davis, editors, pp. 159-175, Pleunum Press, 1986; Human Transbuccal Absorption of Diclofenac Sodium from a Prototype Hydrogel Delivery Device, J. Cassidy et al., published in Pharmaceutical Research, Vol. 10, No. 1, 1993, pp. 126-129; and a recent announcement by 3M of a transmucosal patch. There are a number of major advantages to delivering pharmaceuticals transmucosally in a buccal tablet as opposed to oral delivery in a conventional pill which is swallowed. Some of these advantages are recognized by the pharmaceutical industry and/or physicians, and others may not be. Those that are believed to be recognized by others are described immediately below, and those that are not are described further below. Also, although a particular advantage of the buccal administration of drugs may be known, the application of that advantage to a particular pharmaceutical or class of pharmaceuticals may not be known.
Two advantages of buccal administration are currently recognized commercially or in the medical literature. The first known advantage is rapidity of action. Medications administered bucally enter the blood stream immediately after passage through the buccal mucosa instead of first having to be swallowed and then having to pass through a portion of the gastrointestinal tract before being absorbed. This rapidity of action is one of the reasons that one commercially available and one experimental product for pain relief have been administered via the buccal route. The first of these products contains nitroglyerin, and is available as a buccal pill that adheres to the mucosa, sold under the trademark Nitrogard. The second product contains the non-steroidal anti-inflammatory analgesic diclofenac which has been used in an experimental buccal pill that adheres to the mucosa (see previous reference by J. Cassidy). The second known advantage of the buccal route is to allow administration of medications which cannot normally be administered orally. Additional unique advantages of the buccal route and the medications that exploit these advantages are described below, as well as additional medications that could be administered buccally to exploit the two previously mentioned advantages of the buccal route.
The buccal tablets and patches described so far were adhered to the cheek or the gum, and provided for direct delivery of the pharmaceutical carried by the tablet or patch through only a single mucosa, either the mucosa to which the tablet or patch was adhered or the mucosa opposite thereto. Buccal tablets and patches, which must remain in the mouth for a particular length of time in order to transmucosally deliver a therapeutically effective amount of the pharmaceutical, suffer from the competing constraints that they contain a relatively large amount of the pharmaceutical and yet be small enough stay in the mouth for hours at a time with minimum discomfort, and without moving and risk of being swallowed. Additionally, the tablet or patch should be maintained in direct contact with a mucosa to reduce the effects of salivary washout of the pharmaceutical. To that end, the tablets and patches described so far, as mentioned, all have been adhered in the mouth to positively hold them in place adjacent an oral mucosa over long periods of time. The use of an adhesive imposes five limitations on a buccal tablet or patch. First, the adhesive, e.g., a hydrogel self-adhesive, with which such tablets are adhered in the mouth may inflame or damage the buccal mucosa over prolonged use. Even though such damage may not result in health problems in the mouth, it may interfere with absorption of a pharmaceutical particularly with prolonged use. Secondly, the use of an adhesive limits absorption to only one mucosal surface, the one to which the adhesive is attached. Thirdly, the adhesive, unless it is permeable, reduces the amount of surface area available for drug absorption across the one mucosal surface in contact with the buccal tablet. Fourthly, the use of an adhesive adds to the complexity and expense of fabricating a buccal tablet. Fifthly, the use of an adhesive system reduces the volume of the buccal tablet that can be devoted to containing the drug and thus reduces its drug capacity.
There is therefore a need for devices that will deliver a therapeutically-effective amount of a pharmaceutical transmucosally which have one and preferably more of the following characteristics: are relatively small; contain a relatively large amount of the pharmaceutical; may remain in the mouth for long periods of time without moving and with little or no discomfort and without damaging the buccal mucosa, can deliver the pharmaceutical relatively quickly; can sustain delivery of therapeutically effective levels of a pharmaceutical over time; can allow a greater amount of mucosal surface to be used for absorption than previously described buccal tablets or patches; and is simple and inexpensive to fabricate.